Gene Symbol: HERC2
Description: HECT and RLD domain containing E3 ubiquitin protein ligase 2
Alias: D15F37S1, MRT38, SHEP1, jdf2, p528, E3 ubiquitin-protein ligase HERC2, HECT-type E3 ubiquitin transferase HERC2, hect domain and RCC1-like domain-containing protein 2, hect domain and RLD 2
Species: human
Products:     HERC2

Top Publications

  1. Ji Y, Walkowicz M, Buiting K, Johnson D, Tarvin R, Rinchik E, et al. The ancestral gene for transcribed, low-copy repeats in the Prader-Willi/Angelman region encodes a large protein implicated in protein trafficking, which is deficient in mice with neuromuscular and spermiogenic abnormalities. Hum Mol Genet. 1999;8:533-42 pubmed
    ..We report here the identification of the ancestral gene ( HERC2 ) and a family of duplicated, truncated copies that comprise these low-copy repeats...
  2. Kayser M, Liu F, Janssens A, Rivadeneira F, Lao O, van Duijn K, et al. Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene. Am J Hum Genet. 2008;82:411-23 pubmed publisher
    ..Single nucleotide polymorphisms (SNPs) in the HERC2 gene and, to a lesser extent, in the neighboring OCA2 gene were independently associated to iris color variation...
  3. Branicki W, Brudnik U, Wojas Pelc A. Interactions between HERC2, OCA2 and MC1R may influence human pigmentation phenotype. Ann Hum Genet. 2009;73:160-70 pubmed publisher
    ..Recent studies have revealed that interactive effects between HERC2 and OCA2 may be responsible for blue eye colour determination in humans...
  4. Branicki W, Liu F, van Duijn K, Draus Barini J, Pośpiech E, Walsh S, et al. Model-based prediction of human hair color using DNA variants. Hum Genet. 2011;129:443-54 pubmed publisher
  5. Wu W, Sato K, Koike A, Nishikawa H, Koizumi H, Venkitaraman A, et al. HERC2 is an E3 ligase that targets BRCA1 for degradation. Cancer Res. 2010;70:6384-92 pubmed publisher
    ..Here, we show that HERC2, a protein recently implicated in DNA damage repair, targets BARD1-uncoupled BRCA1 for degradation...
  6. Liu F, Wollstein A, Hysi P, Ankra Badu G, Spector T, Park D, et al. Digital quantification of human eye color highlights genetic association of three new loci. PLoS Genet. 2010;6:e1000934 pubmed publisher
    ..A model for predicting quantitative eye colors explained over 50% of trait variance in the Rotterdam Study. Over all our data exemplify that fine phenotyping is a useful strategy for finding genes involved in human complex traits. ..
  7. Mengel From J, Børsting C, Sanchez J, Eiberg H, Morling N. Human eye colour and HERC2, OCA2 and MATP. Forensic Sci Int Genet. 2010;4:323-8 pubmed publisher
    ..Strong associations between blue/brown eye colour and the SNP loci rs1129038 and rs12913832 in the HERC2 gene were recently described. Weaker associations between eye colour and other genetic markers also exist...
  8. Bekker Jensen S, Rendtlew Danielsen J, Fugger K, Gromova I, Nerstedt A, Lukas C, et al. HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes. Nat Cell Biol. 2010;12:80-6; sup pp 1-12 pubmed publisher
    ..Here, we identify HERC2 as a factor that regulates ubiquitin-dependent retention of repair proteins on damaged chromosomes...
  9. Han J, Kraft P, Nan H, Guo Q, Chen C, Qureshi A, et al. A genome-wide association study identifies novel alleles associated with hair color and skin pigmentation. PLoS Genet. 2008;4:e1000074 pubmed publisher
    ..52). One variant in the MATP gene was associated with hair color. A variant in the HERC2 gene upstream of the OCA2 gene showed the strongest and independent association with hair color compared with ..

More Information


  1. Danielsen J, Povlsen L, Villumsen B, Streicher W, Nilsson J, Wikström M, et al. DNA damage-inducible SUMOylation of HERC2 promotes RNF8 binding via a novel SUMO-binding Zinc finger. J Cell Biol. 2012;197:179-87 pubmed publisher
    ..ubiquitylation of chromatin surrounding deoxyribonucleic acid (DNA) double-strand breaks (DSBs) by the RNF8/RNF168/HERC2 ubiquitin ligases facilitates restoration of genome integrity by licensing chromatin to concentrate genome ..
  2. Sturm R, Duffy D, Zhao Z, Leite F, Stark M, Hayward N, et al. A single SNP in an evolutionary conserved region within intron 86 of the HERC2 gene determines human blue-brown eye color. Am J Hum Genet. 2008;82:424-31 pubmed publisher
    ..fine association mapping of eye color SNPs in the intergenic region upstream of OCA2 and within the neighboring HERC2 (hect domain and RLD2) gene...
  3. Sulem P, Gudbjartsson D, Stacey S, Helgason A, Rafnar T, Magnusson K, et al. Genetic determinants of hair, eye and skin pigmentation in Europeans. Nat Genet. 2007;39:1443-52 pubmed
    ..3 is associated with freckles. The fifth region provided refinements to a previously reported association in OCA2, and the sixth encompasses previously described variants in MC1R. ..
  4. Martinez Noel G, Galligan J, Sowa M, Arndt V, Overton T, Harper J, et al. Identification and proteomic analysis of distinct UBE3A/E6AP protein complexes. Mol Cell Biol. 2012;32:3095-106 pubmed publisher
    ..With the exception of HERC2, which modulates the ubiquitin ligase activity of E6AP, little is known about the regulation or function of E6AP ..
  5. Shekar S, Duffy D, Frudakis T, Sturm R, Zhao Z, Montgomery G, et al. Linkage and association analysis of spectrophotometrically quantified hair color in Australian adolescents: the effect of OCA2 and HERC2. J Invest Dermatol. 2008;128:2807-14 pubmed publisher
    ..03 after correction for multiple testing, respectively). These two SNPs explain 1.54 and 0.85% of variation in the A650t index, respectively. ..
  6. Izawa N, Wu W, Sato K, Nishikawa H, Kato A, Boku N, et al. HERC2 Interacts with Claspin and regulates DNA origin firing and replication fork progression. Cancer Res. 2011;71:5621-5 pubmed publisher
    ..b>HERC2, a large HECT protein required for homologous recombination repair, is an E3 ubiquitin ligase that targets breast ..
  7. Eiberg H, Troelsen J, Nielsen M, Mikkelsen A, Mengel From J, Kjaer K, et al. Blue eye color in humans may be caused by a perfectly associated founder mutation in a regulatory element located within the HERC2 gene inhibiting OCA2 expression. Hum Genet. 2008;123:177-87 pubmed publisher
    ..linkage analysis of a large Danish family, we finemapped the blue eye color locus to a 166 Kbp region within the HERC2 gene...
  8. Zaorska K, Zawierucha P, Nowicki M. Prediction of skin color, tanning and freckling from DNA in Polish population: linear regression, random forest and neural network approaches. Hum Genet. 2019;: pubmed publisher
    ..8% correct calls, AUC = 0.537 for freckling prediction). Our study confirms the association of rs12913832 (HERC2) with all three skin pigmentation traits, but also variants associated solely with certain pigmentation traits, ..
  9. Xiao F, Ma J, Cai G, Fang S, Lee J, Wei Q, et al. Natural and orthogonal model for estimating gene-gene interactions applied to cutaneous melanoma. Hum Genet. 2014;133:559-74 pubmed publisher
    ..Although associated genes have been identified for predisposing people to melanoma risk: HERC2 at 15q13.1, MC1R at 16q24.3 and CDKN2A at 9p21...
  10. Yucesoy B, Kaufman K, Lummus Z, Weirauch M, Zhang G, Cartier A, et al. Genome-Wide Association Study Identifies Novel Loci Associated With Diisocyanate-Induced Occupational Asthma. Toxicol Sci. 2015;146:192-201 pubmed publisher
    ..the strongest association was for the rs12913832 SNP located on chromosome 15, which has been mapped to the HERC2 gene (p = 6.94 × 10(-14))...
  11. Adhikari K, Mendoza Revilla J, Sohail A, Fuentes Guajardo M, Lampert J, Chacón Duque J, et al. A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigmentation in Eurasia. Nat Commun. 2019;10:358 pubmed publisher
    ..of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles...
  12. Zhu D, Yang D, Li X, Feng F. Heterogeneous expression and biological function of SOX18 in osteosaroma. J Cell Biochem. 2018;119:4184-4192 pubmed publisher
    ..HERC3, HERC4, HERC5, and HERC6 in OS patients and in OS cells, with the most significant correlation detected in HERC2 expression, which was following found interacted with SOX18 in OS cells...
  13. Cubillos Rojas M, Schneider T, Hadjebi O, Pedrazza L, de Oliveira J, Langa F, et al. The HERC2 ubiquitin ligase is essential for embryonic development and regulates motor coordination. Oncotarget. 2016;7:56083-56106 pubmed publisher
    A mutation in the HERC2 gene has been linked to a severe neurodevelopmental disorder with similarities to the Angelman syndrome...
  14. Sitek A, Rosset I, Zadzińska E, Siewierska Górska A, Pietrowska E, Strapagiel D. Selected gene polymorphisms effect on skin and hair pigmentation in Polish children at the prepubertal age. Anthropol Anz. 2016;73:283-293 pubmed
    ..2-q12), rs35264875 (TPCN2-11q13.3), rs16891982 (SLC45A2-5p13.2), rs12913832 (HERC2-15q13) and rs1805007 (MC1R-16q24.3)...
  15. Wu W, Rokutanda N, Takeuchi J, Lai Y, Maruyama R, Togashi Y, et al. HERC2 Facilitates BLM and WRN Helicase Complex Interaction with RPA to Suppress G-Quadruplex DNA. Cancer Res. 2018;78:6371-6385 pubmed publisher
    BLM and WRN are RecQ DNA helicasesessential for genomic stability. Here, we demonstrate that HERC2, a HECT E3 ligase, is critical for their functions to suppress G-quadruplex (G4) DNA...
  16. Shah R, Guggenheim J. Genome-wide association studies for corneal and refractive astigmatism in UK Biobank demonstrate a shared role for myopia susceptibility loci. Hum Genet. 2018;137:881-896 pubmed publisher
    ..3), HERC2/OCA2 (15q13.1) and NPLOC4/TSPAN10 (17q25.3)...
  17. Walkowicz M, Ji Y, Ren X, Horsthemke B, Russell L, Johnson D, et al. Molecular characterization of radiation- and chemically induced mutations associated with neuromuscular tremors, runting, juvenile lethality, and sperm defects in jdf2 mice. Mamm Genome. 1999;10:870-8 pubmed
    ..Recent work has demonstrated that the jdf2 phenotype is associated with deletions and point mutations in Herc2, a gene encoding an exceptionally large guanine nucleotide exchange factor protein thought to play a role in ..
  18. Mohiuddin -, Kobayashi S, Keka I, Guilbaud G, Sale J, Narita T, et al. The role of HERC2 and RNF8 ubiquitin E3 ligases in the promotion of translesion DNA synthesis in the chicken DT40 cell line. DNA Repair (Amst). 2016;40:67-76 pubmed publisher
    ..The HERC2 ubiquitin ligase plays a role in homologous recombination by facilitating the assembly of the Ubc13 ubiquitin-..
  19. Barón A, Asdigian N, Gonzalez V, Aalborg J, Terzian T, Stiegmann R, et al. Interactions between ultraviolet light and MC1R and OCA2 variants are determinants of childhood nevus and freckle phenotypes. Cancer Epidemiol Biomarkers Prev. 2014;23:2829-39 pubmed publisher
    ..MC1R and HERC2/OCA2 rs12913832 were genotyped and linear mixed models were used to identify main and interaction effects...
  20. Liu F, Visser M, Duffy D, Hysi P, Jacobs L, Lao O, et al. Genetics of skin color variation in Europeans: genome-wide association studies with functional follow-up. Hum Genet. 2015;134:823-35 pubmed publisher
    ..In addition, genomic loci at 5p13.2 (SLC45A2), 6p25.3 (IRF4), 15q13.1 (HERC2/OCA2), and 16q24.3 (MC1R) were confirmed to be involved in skin coloration in Europeans...
  21. Galligan J, Martinez Noël G, Arndt V, Hayes S, Chittenden T, Harper J, et al. Proteomic analysis and identification of cellular interactors of the giant ubiquitin ligase HERC2. J Proteome Res. 2015;14:953-66 pubmed publisher
    b>HERC2 is a large E3 ubiquitin ligase with multiple structural domains that has been implicated in an array of cellular processes...
  22. Lim J, Song M, Cho Y, Kim W, Han S, Ryu J. Comparative analysis of microRNA and mRNA expression profiles in cells and exosomes under toluene exposure. Toxicol In Vitro. 2017;41:92-101 pubmed publisher
    ..the eight putative target genes of the differentially expressed miRNAs under toluene exposure (EXOSC6, RHOH, GFER, HERC2, GOLGA4, SLC7A11, GCLM, and BACH1) are related to diverse disease categories such as nervous system disease, ..
  23. Xie H, Xue L, Hua W, Jia B, Zhang L, Li L. Whole genome sequencing and 6-year follow-up of a mother and daughter with frontometaphyseal dysplasia associated with keratitis, xerosis, poikiloderma, and acro-osteolysis: A case report. Medicine (Baltimore). 2018;97:e11283 pubmed publisher
    ..of cutaneous neoplasms and absence of classical XP features, WGS didn't find supportive genetical evidence, but 2 HERC2 variants were assigned highest suspicion in both XP and SCC by bioinformatical analyses...
  24. Siewierska Górska A, Sitek A, Żądzińska E, Bartosz G, Strapagiel D. Association of five SNPs with human hair colour in the Polish population. Homo. 2017;68:134-144 pubmed publisher
    Twenty-two variants (single nucleotide polymorphisms - SNPs) of the genes involved in hair pigmentation (OCA2, HERC2, MC1R, SLC24A5, SLC45A2, TPCN2, TYR, TYRP1) were genotyped in a group of 186 Polish participants, representing a range ..
  25. Johansson P, Klein Hitpass L, Choidas A, Habenberger P, Mahboubi B, Kim B, et al. SAMHD1 is recurrently mutated in T-cell prolymphocytic leukemia. Blood Cancer J. 2018;8:11 pubmed publisher
    ..We identified recurrently mutated genes previously unknown to be mutated in T-PLL, which are SAMHD1, HERC1, HERC2, PRDM2, PARP10, PTPRC, and FOXP1...
  26. Suh Y, Choe J, Park H. Malignancy in Pheochromocytoma or Paraganglioma: Integrative Analysis of 176 Cases in TCGA. Endocr Pathol. 2017;28:159-164 pubmed publisher
    ..5, HERC2, SETD2, TGDS, TRHDE, FKBP9, and BMS1...
  27. Herbin O, Regelmann A, Ramkhelawon B, Weinstein E, Moore K, Alexandropoulos K. Monocyte Adhesion and Plaque Recruitment During Atherosclerosis Development Is Regulated by the Adapter Protein Chat-H/SHEP1. Arterioscler Thromb Vasc Biol. 2016;36:1791-801 pubmed publisher
    ..cell-specific adaptor protein Cas- and Hef1-associated signal transducer hematopoietic isoform (Chat-H)/SHEP1 regulated lymphocyte adhesion and migration...
  28. Sánchez Tena S, Cubillos Rojas M, Schneider T, Rosa J. Functional and pathological relevance of HERC family proteins: a decade later. Cell Mol Life Sci. 2016;73:1955-68 pubmed publisher
    ..Whereas large HERCs (HERC1 and HERC2) contain one HECT and more than one RLD, small HERCs (HERC3-6) possess single HECT and RLD domains...
  29. Chicard M, Colmet Daage L, Clement N, Danzon A, Bohec M, Bernard V, et al. Whole-Exome Sequencing of Cell-Free DNA Reveals Temporo-spatial Heterogeneity and Identifies Treatment-Resistant Clones in Neuroblastoma. Clin Cancer Res. 2018;24:939-949 pubmed publisher
    ..with concomitant disappearance of other clones was identified by a mutation in the ubiquitin protein ligase HERC2Conclusions: Modelization of mutated allele fractions in cfDNA indicated distinct patterns of clonal ..
  30. Ji Y, Rebert N, Joslin J, Higgins M, Schultz R, Nicholls R. Structure of the highly conserved HERC2 gene and of multiple partially duplicated paralogs in human. Genome Res. 2000;10:319-29 pubmed
    ..We identified previously the large HERC2 transcript as an ancestral gene in this duplicon, with approximately 11 HERC2-containing duplicons, and ..
  31. Kühnle S, Kogel U, Glockzin S, Marquardt A, Ciechanover A, Matentzoglu K, et al. Physical and functional interaction of the HECT ubiquitin-protein ligases E6AP and HERC2. J Biol Chem. 2011;286:19410-6 pubmed publisher
    ..In this study, we report that the giant protein HERC2, which is like E6AP a member of the HECT family of ubiquitin-protein ligases, binds to E6AP...
  32. Saez I, Koyuncu S, Gutiérrez García R, Dieterich C, Vilchez D. Insights into the ubiquitin-proteasome system of human embryonic stem cells. Sci Rep. 2018;8:4092 pubmed publisher
    ..Among them, we find HECT-domain E3 ligases such as HERC2 and UBE3A as well as several RING-domain E3s, including UBR7 and RNF181...
  33. Bai B, Man A, Yang K, Guo Y, Xu C, Tse H, et al. Endothelial SIRT1 prevents adverse arterial remodeling by facilitating HERC2-mediated degradation of acetylated LKB1. Oncotarget. 2016;7:39065-39081 pubmed publisher
    ..Results-Co-immunoprecipitation assay demonstrated that SIRT1, via its amino-terminus, binds to the DOC domain of HERC2 [HECT and RLD domain containing E3 ubiquitin protein ligase 2], which then ubiquitinates LKB1 in the nuclear ..
  34. Zhang M, Song F, Liang L, Nan H, Zhang J, Liu H, et al. Genome-wide association studies identify several new loci associated with pigmentation traits and skin cancer risk in European Americans. Hum Mol Genet. 2013;22:2948-59 pubmed publisher
    ..0 × 10(-8); P = 6.6 × 10(-7) in the discovery set and P = 3.0 × 10(-3) in the replication set) and rs8015138 upstream of GNG2 (P = 6.6 × 10(-8); P = 5.3 × 10(-7) in the discovery set and P = 0.01 in the replication set). ..
  35. Chan N, den Besten W, Sweredoski M, Hess S, Deshaies R, Chan D. Degradation of the deubiquitinating enzyme USP33 is mediated by p97 and the ubiquitin ligase HERC2. J Biol Chem. 2014;289:19789-98 pubmed publisher
    ..The p97 adaptor complex involved in this function is the Ufd1-Npl4 heterodimer. Furthermore, we identified HERC2, a HECT domain-containing E3 ligase, as being responsible for polyubiquitination of USP33...
  36. Martinez Noel G, Luck K, Kühnle S, Desbuleux A, Szajner P, Galligan J, et al. Network Analysis of UBE3A/E6AP-Associated Proteins Provides Connections to Several Distinct Cellular Processes. J Mol Biol. 2018;430:1024-1050 pubmed publisher
    ..Previously, we showed that UBE3A associates with HERC2, NEURL4, and MAPK6/ERK3 in a high-molecular-weight complex of unknown function that we refer to as the HUN complex ..
  37. Lin B, Mbarek H, Willemsen G, Dolan C, Fedko I, Abdellaoui A, et al. Heritability and Genome-Wide Association Studies for Hair Color in a Dutch Twin Family Based Sample. Genes (Basel). 2015;6:559-76 pubmed publisher
    ..Five other known genes (HERC2, TPCN2, SLC24A4, IRF4, and KITLG) gave genome-wide significant hits for blond, brown and light versus dark hair ..
  38. Park J, Kang T. Transcriptional and Posttranslational Regulation of Nucleotide Excision Repair: The Guardian of the Genome against Ultraviolet Radiation. Int J Mol Sci. 2016;17: pubmed
    ..domain (RLD) and homologous to the E6-AP carboxyl terminus (HECT) domain containing E3 ubiquitin protein ligase 2 (HERC2). In this review we highlight recent data on the transcriptional and posttranslational regulation of NER activity.
  39. Bonanno L, Costa C, Majem M, Sanchez J, Rodriguez I, Gimenez Capitan A, et al. Combinatory effect of BRCA1 and HERC2 expression on outcome in advanced non-small-cell lung cancer. BMC Cancer. 2016;16:312 pubmed publisher
    ..Several proteins modulate the function of BRCA1. The E3 ubiquitin ligase HERC2 facilitates the assembly of the RNF8-UBC13 complex to recruit BRCA1 to DNA damage sites...
  40. García Heredia J, Carnero A. The cargo protein MAP17 (PDZK1IP1) regulates the immune microenvironment. Oncotarget. 2017;8:98580-98597 pubmed publisher
    ..i>MAP17 expression correlated also with the markers of inflammation HLAs, BBS10, HERC2, ADNP and PYCARD...
  41. Cubillos Rojas M, Amair Pinedo F, Peiró Jordán R, Bartrons R, Ventura F, Rosa J. The E3 ubiquitin protein ligase HERC2 modulates the activity of tumor protein p53 by regulating its oligomerization. J Biol Chem. 2014;289:14782-95 pubmed publisher
    ..Here we report that the HECT E3 ubiquitin ligase HERC2 interacts with p53...
  42. Zhu M, Zhao H, Liao J, Xu X. HERC2/USP20 coordinates CHK1 activation by modulating CLASPIN stability. Nucleic Acids Res. 2014;42:13074-81 pubmed publisher
    ..Under unperturbed conditions, the E3 ubiquitin ligase HERC2 regulates the stability of the deubiquitinating enzyme USP20 by promoting ubiquitination-mediated proteasomal ..
  43. Harlalka G, Baple E, Cross H, Kühnle S, Cubillos Rojas M, Matentzoglu K, et al. Mutation of HERC2 causes developmental delay with Angelman-like features. J Med Genet. 2013;50:65-73 pubmed publisher
    ..The ubiquitin ligase HERC2, encoded by the HERC2 gene is thought to be a key regulator of E6AP...
  44. Valnegri P, Huang J, Yamada T, Yang Y, Mejia L, Cho H, et al. RNF8/UBC13 ubiquitin signaling suppresses synapse formation in the mammalian brain. Nat Commun. 2017;8:1271 pubmed publisher
    ..Proteomics analyses reveal that neuronal RNF8 interacts with the HECT domain protein HERC2 and scaffold protein NEURL4, and knockdown of HERC2 or NEURL4 phenocopies the inhibition of RNF8/UBC13 signaling ..
  45. Cubillos Rojas M, Schneider T, Bartrons R, Ventura F, Rosa J. NEURL4 regulates the transcriptional activity of tumor suppressor protein p53 by modulating its oligomerization. Oncotarget. 2017;8:61824-61836 pubmed publisher
    ..The E3 ubiquitin ligase HERC2 controls the p53 transcriptional activity by regulation of its oligomerization state...
  46. Pośpiech E, Karłowska Pik J, Ziemkiewicz B, Kukla M, Skowron M, Wojas Pelc A, et al. Further evidence for population specific differences in the effect of DNA markers and gender on eye colour prediction in forensics. Int J Legal Med. 2016;130:923-34 pubmed publisher
    ..arises from evaluation of the currently available eye colour prediction markers shows that only the analysis of HERC2-OCA2 complex has similar effectiveness in different populations, while the predictive potential of other loci may ..
  47. Wang K, Baldassano R, Zhang H, Qu H, Imielinski M, Kugathasan S, et al. Comparative genetic analysis of inflammatory bowel disease and type 1 diabetes implicates multiple loci with opposite effects. Hum Mol Genet. 2010;19:2059-67 pubmed publisher
    ..including known CD loci (ICOSLG and TNFSF15) and T1D loci (TNFAIP3) that confer UC risk, known UC loci (HERC2 and IL26) that confer T1D risk and known UC loci (IL10 and CCNY) that confer CD risk...
  48. Wang S, Kollipara R, Humphries C, Ma S, Hutchinson R, Li R, et al. The ubiquitin ligase TRIM25 targets ERG for degradation in prostate cancer. Oncotarget. 2016;7:64921-64931 pubmed publisher
    ..Thus, overexpression of ERG in prostate cancer may cause an increase in TRIM25 activity, which is mitigated by the expression of the deubiquitinase USP9X, which is required to stabilize ERG. ..
  49. Zhang Z, Yang H, Wang H. The histone H2A deubiquitinase USP16 interacts with HERC2 and fine-tunes cellular response to DNA damage. J Biol Chem. 2014;289:32883-94 pubmed publisher
    ..Here we report that the histone H2A deubiquitinase USP16 interacts with HERC2, fine-tunes the ubiquitin signal during repair, and importantly, is required for terminating the ubiquitination ..
  50. Anderson C, Massey D, Barrett J, Prescott N, Tremelling M, Fisher S, et al. Investigation of Crohn's disease risk loci in ulcerative colitis further defines their molecular relationship. Gastroenterology. 2009;136:523-9.e3 pubmed publisher
    ..ECM1 variation was not associated with CD. Collectively, these data help define the genetic relationship between CD and UC and characterize common, as well as disease-specific mechanisms of pathogenesis. ..
  51. Jin Y, Birlea S, Fain P, Ferrara T, Ben S, Riccardi S, et al. Genome-wide association analyses identify 13 new susceptibility loci for generalized vitiligo. Nat Genet. 2012;44:676-80 pubmed publisher
    ..These include OCA2-HERC2 (combined P = 3.80 × 10(-8)), MC1R (P = 1.82 × 10(-13)), a region near TYR (P = 1.57 × 10(-13)), IFIH1 (P = 4...
  52. Azoitei N, Hoffmann C, Ellegast J, Ball C, Obermayer K, Gößele U, et al. Targeting of KRAS mutant tumors by HSP90 inhibitors involves degradation of STK33. J Exp Med. 2012;209:697-711 pubmed publisher
  53. Cleynen I, Mahachie John J, Henckaerts L, Van Moerkercke W, Rutgeerts P, Van Steen K, et al. Molecular reclassification of Crohn's disease by cluster analysis of genetic variants. PLoS ONE. 2010;5:e12952 pubmed publisher
    ..The used technique can be applied to other common complex diseases as well, and will help to complete patient characterization, in order to evolve towards personalized medicine. ..
  54. Kang T, Lindsey Boltz L, Reardon J, Sancar A. Circadian control of XPA and excision repair of cisplatin-DNA damage by cryptochrome and HERC2 ubiquitin ligase. Proc Natl Acad Sci U S A. 2010;107:4890-5 pubmed publisher
    ..of transcription by the core circadian clock proteins including cryptochrome and by regulation at the posttranslational level by the HERC2 ubiquitin ligase. These findings may be used as a guide for timing of cisplatin chemotherapy.
  55. Moskvina V, Smith M, Ivanov D, Blackwood D, Stclair D, Hultman C, et al. Genetic differences between five European populations. Hum Hered. 2010;70:141-9 pubmed publisher
    ..top loci span genes that have already been reported as highly stratified: genes for hair color and pigmentation (HERC2, EXOC2, IRF4), the LCT gene, genes involved in NAD metabolism, and in immunity (HLA and the Toll-like receptor ..
  56. Ibarrola Villava M, Fernandez L, Pita G, Bravo J, Floristan U, Sendagorta E, et al. Genetic analysis of three important genes in pigmentation and melanoma susceptibility: CDKN2A, MC1R and HERC2/OCA2. Exp Dermatol. 2010;19:836-44 pubmed publisher
    ..In addition, three potentially functional SNPs were selected in p16/CDKN2A and in the promoter region of OCA2/HERC2. Our data for CDKN2A gene did not reach statistically significant results for any of the two studied alleles...
  57. Sheng Y, Hong J, Doherty R, Srikumar T, Shloush J, Avvakumov G, et al. A human ubiquitin conjugating enzyme (E2)-HECT E3 ligase structure-function screen. Mol Cell Proteomics. 2012;11:329-41 pubmed publisher
    ..Our data set represents the first comprehensive analysis of E2-HECT E3 interactions, and thus provides a framework for better understanding the molecular mechanisms of ubiquitylation. ..
  58. Andrade E, Fracasso N, Strazza Júnior P, Simoes A, Mendes Junior C. Associations of OCA2-HERC2 SNPs and haplotypes with human pigmentation characteristics in the Brazilian population. Leg Med (Tokyo). 2017;24:78-83 pubmed publisher
    ..We evaluated the association of seven OCA2-HERC2 SNPs and haplotypes with pigmentation characteristics (eye, skin, hair and freckles) in the highly admixed and ..
  59. Yoo N, Park S, Lee S. Frameshift mutations of ubiquitination-related genes HERC2, HERC3, TRIP12, UBE2Q1 and UBE4B in gastric and colorectal carcinomas with microsatellite instability. Pathology. 2011;43:753-5 pubmed publisher
  60. Weersma R, Stokkers P, Cleynen I, Wolfkamp S, Henckaerts L, Schreiber S, et al. Confirmation of multiple Crohn's disease susceptibility loci in a large Dutch-Belgian cohort. Am J Gastroenterol. 2009;104:630-8 pubmed publisher
    ..09 E-04) and Hect domain and RCC1-like domain 2 (HERC2; rs916977, P=1.12E-04). Pooling our data with the original WTCCC data substantiated these associations...
  61. Guerra Rebollo M, Mateo F, Franke K, Huen M, Lopitz Otsoa F, Rodriguez M, et al. Nucleolar exit of RNF8 and BRCA1 in response to DNA damage. Exp Cell Res. 2012;318:2365-76 pubmed publisher
  62. Mancias J, Pontano Vaites L, Nissim S, Biancur D, Kim A, Wang X, et al. Ferritinophagy via NCOA4 is required for erythropoiesis and is regulated by iron dependent HERC2-mediated proteolysis. elife. 2015;4: pubmed publisher
    ..NCOA4 turnover is promoted by excess iron and involves an iron-dependent interaction between NCOA4 and the HERC2 ubiquitin ligase. In zebrafish and cultured cells, NCOA4 plays an essential role in erythroid differentiation...
  63. Lee T, Park J, Leem S, Kang T. Coordinated regulation of XPA stability by ATR and HERC2 during nucleotide excision repair. Oncogene. 2014;33:19-25 pubmed publisher
    ..Here we show that ATR-mediated XPA phosphorylation enhances XPA stability by inhibiting HERC2-mediated ubiquitination and subsequent degradation...
  64. Weinhold N, Johnson D, Chubb D, Chen B, Forsti A, Hosking F, et al. The CCND1 c.870G>A polymorphism is a risk factor for t(11;14)(q13;q32) multiple myeloma. Nat Genet. 2013;45:522-525 pubmed publisher
    ..870G>A polymorphism (P = 7.96 × 10(-11)). These results provide a model in which a constitutive genetic factor is associated with risk of a specific chromosomal translocation. ..
  65. Caliebe A, Harder M, Schuett R, Krawczak M, Nebel A, von Wurmb Schwark N. The more the merrier? How a few SNPs predict pigmentation phenotypes in the Northern German population. Eur J Hum Genet. 2016;24:739-47 pubmed publisher
    ..Our study comprised two samples of 300 and 100 individuals from Northern Germany. SNP rs12913832 in HERC2 was found to be strongly associated with blue eye colour (odds ratio=40.0, P<1...
  66. Iida R, Ueki M, Takeshita H, Fujihara J, Nakajima T, Kominato Y, et al. Genotyping of five single nucleotide polymorphisms in the OCA2 and HERC2 genes associated with blue-brown eye color in the Japanese population. Cell Biochem Funct. 2009;27:323-7 pubmed publisher
    ..rs7495174, rs4778241, rs4778138) and two SNPs in intron 86 (rs12913832) and the 3' UTR region (rs1129038) of the HERC2 gene--located in the upstream of the OCA2 locus--have a high statistical association with human eye color...
  67. Visser M, Kayser M, Palstra R. HERC2 rs12913832 modulates human pigmentation by attenuating chromatin-loop formation between a long-range enhancer and the OCA2 promoter. Genome Res. 2012;22:446-55 pubmed publisher
    ..It is located within an intron of the nonpigment gene HERC2, 21 kb upstream of the pigment gene OCA2, and the region surrounding rs12913832 is highly conserved among animal ..
  68. Puffenberger E, Jinks R, Wang H, Xin B, Fiorentini C, Sherman E, et al. A homozygous missense mutation in HERC2 associated with global developmental delay and autism spectrum disorder. Hum Mutat. 2012;33:1639-46 pubmed publisher
    ..6 Mb and excluded one of the two novel homozygous exome variants. The remaining variant, a missense change in HERC2 (c.1781C>T, p.Pro594Leu), occurs in a highly conserved proline residue within an RCC1-like functional domain...
  69. Peng Y, Dai H, Wang E, Lin C, Mo W, Peng G, et al. TUSC4 functions as a tumor suppressor by regulating BRCA1 stability. Cancer Res. 2015;75:378-86 pubmed publisher
    ..Mechanistic investigations indicated that TUSC4 protein could physically interact with the E3 ligase Herc2, which prevents BRCA1 degradation through the ubiquitination pathway...
  70. Crawford N, Kelly D, Hansen M, Beltrame M, Fan S, Bowman S, et al. Loci associated with skin pigmentation identified in African populations. Science. 2017;358: pubmed publisher
    ..we identify variants in or near SLC24A5, MFSD12, DDB1, TMEM138, OCA2, and HERC2 that are significantly associated with skin pigmentation...
  71. Sankaran J, Varshney M, Judex S. Differences in bone structure and unloading-induced bone loss between C57BL/6N and C57BL/6J mice. Mamm Genome. 2017;28:476-486 pubmed publisher
    ..mice, giving rise to a differential response to mechanical unloading that may be modulated, in part, by the genes Herc2, Myo18b, and Acan...
  72. Wei L, Allain D, Bernhardt M, Gillespie J, Peters S, Iwenofu O, et al. Variants at the OCA2/HERC2 locus affect time to first cutaneous squamous cell carcinoma in solid organ transplant recipients collected using two different study designs. Br J Dermatol. 2017;177:1066-1073 pubmed publisher
    Variants at the oculocutaneous albinism 2 (OCA2)/HECT and RLD domain containing E3 ubiquitin protein ligase 2 (HERC2) locus have been associated with pigmentation phenotypes and risk of developing several types of skin cancer.
  73. Imai Y, Kobayashi Y, Inoshita T, Meng H, Arano T, Uemura K, et al. The Parkinson's Disease-Associated Protein Kinase LRRK2 Modulates Notch Signaling through the Endosomal Pathway. PLoS Genet. 2015;11:e1005503 pubmed publisher
    ..We have identified two novel LRRK2-associated proteins, a HECT-type ubiquitin ligase, HERC2, and an adaptor-like protein with six repeated Neuralized domains, NEURL4...
  74. Elia A, Wang D, Willis N, Boardman A, Hajdu I, Adeyemi R, et al. RFWD3-Dependent Ubiquitination of RPA Regulates Repair at Stalled Replication Forks. Mol Cell. 2015;60:280-93 pubmed publisher
    ..Multisite protein group sumoylation is known to promote HR in yeast. Our findings reveal a similar requirement for multisite protein group ubiquitination during HR at stalled forks in mammalian cells. ..
  75. Morice Picard F, Benard G, Rezvani H, Lasseaux E, Simon D, Moutton S, et al. Complete loss of function of the ubiquitin ligase HERC2 causes a severe neurodevelopmental phenotype. Eur J Hum Genet. 2016;25:52-58 pubmed publisher
    ..We describe a Mauritanian patient harboring a homozygous deletion restricted to two contiguous genes HERC2 and OCA2 and presenting with severe developmental abnormalities...
  76. Ryu M, Duck K, Philpott C. Ferritin iron regulators, PCBP1 and NCOA4, respond to cellular iron status in developing red cells. Blood Cells Mol Dis. 2018;69:75-81 pubmed publisher
    ..during differentiation triggered lysosomal degradation of NCOA4, which was dependent on the E3 ubiquitin ligase HERC2. Thus, developing red blood cells express a series of proteins that both mediate and regulate the flux of iron to ..
  77. Deihim B, Hassanzadeh M, Shafiei Jandaghi N, Amanlou M, Douraghi M. Characterization of the DNA mismatch repair proteins MutS and MutL in a hypermutator Acinetobacter baumannii. Microb Pathog. 2017;113:74-84 pubmed publisher
    ..non-mutator revealed that T272, D278, G457, S528, A533, Y715, and E747 are closely matched with S272, D278, A457, P528, V533, C715, and K747, respectively in non-mutator strain...
  78. Cheng X, Xu C, DeGiorgio M. Fast and robust detection of ancestral selective sweeps. Mol Ecol. 2017;: pubmed publisher
    ..The MCM6/LCT cluster and the SLC45A2 and HERC2 genes are strong outliers, agreeing with previous studies...
  79. Yuan J, Luo K, Deng M, Li Y, Yin P, Gao B, et al. HERC2-USP20 axis regulates DNA damage checkpoint through Claspin. Nucleic Acids Res. 2014;42:13110-21 pubmed publisher
    ..USP20 is phosphorylated by ATR, resulting in disassociation of the E3 ubiquitin ligase HERC2 from USP20 and USP20 stabilization...
  80. Moroishi T, Yamauchi T, Nishiyama M, Nakayama K. HERC2 targets the iron regulator FBXL5 for degradation and modulates iron metabolism. J Biol Chem. 2014;289:16430-41 pubmed publisher
    ..the discovery of proteins that regulate the stability of FBXL5, we identified the large HECT-type ubiquitin ligase HERC2 (HECT and RLD domain containing E3 ubiquitin protein ligase 2) as an FBXL5-associated protein...
  81. Martinez Cadenas C, Peña Chilet M, Ibarrola Villava M, Ribas G. Gender is a major factor explaining discrepancies in eye colour prediction based on HERC2/OCA2 genotype and the IrisPlex model. Forensic Sci Int Genet. 2013;7:453-60 pubmed publisher
    ..This significant gender difference would suggest that there is an as yet unidentified gender-related factor contributing to human eye colour variation. ..
  82. Candille S, Absher D, Beleza S, Bauchet M, McEvoy B, Garrison N, et al. Genome-wide association studies of quantitatively measured skin, hair, and eye pigmentation in four European populations. PLoS ONE. 2012;7:e48294 pubmed publisher
    ..In our two-stage association study, we reproduce the association of rs1667394 at the OCA2/HERC2 locus with eye color but we do not identify new genetic determinants of skin and hair pigmentation supporting the ..
  83. Franke A, Balschun T, Karlsen T, Hedderich J, May S, Lu T, et al. Replication of signals from recent studies of Crohn's disease identifies previously unknown disease loci for ulcerative colitis. Nat Genet. 2008;40:713-5 pubmed publisher
    ..Among these loci, we identified variants in 3p21.31, NKX2-3 and CCNY as susceptibility factors for both diseases, whereas variants in PTPN2, HERC2 and STAT3 were associated only with ulcerative colitis in our sample collection.
  84. Jacobson A, Macfadden A, Wu Z, Peng J, Liu C. Autoregulation of the 26S proteasome by in situ ubiquitination. Mol Biol Cell. 2014;25:1824-35 pubmed publisher
    ..We propose that in situ ubiquitination of the 26S proteasome regulates its activity, which could function to adjust proteasomal activity in response to the alteration of cellular ubiquitination levels. ..